Autoimmune diseases, particularly those that cause hearing loss such as Meniere's disease (MD), are common and often devastating diseases (Paparella, M. M., The Natural Course of Meniere's Disease in Meniere's Disease: Prospectives in the 90s (R. Filipo & M. Barbara eds. 1994) and Lachman, P. J., et al., Clinical Aspects of Immunology (1993)). The main feature of such diseases is the development and persistence of inflammatory processes in the apparent absence of pathogens, leading to destruction of the target tissues. A comprehensive explanation as to the onset or persistence of autoimmune ear diseases such as idiopathic progressive bilateral sensorineural hearing loss, Meniere's disease and other autoimmune inner ear diseases is not known yet known (Paparella, M. and Lachman, P. J., et al.).
Generally, chronic activation of helper T lymphocytes, reactive against self-proteins, appears to be crucial for fueling destructive autoimmune processes. However, antibodies against self proteins as well as molecularly mimicked microbial products are also implicated in some autoimmune diseases. Why certain individuals develop autoimmune diseases is not yet to determined, but genetic and environmental factors are most likely involved. In several autoimmune diseases the causative antigen(s) are not identified or characterized fully since several different self proteins or molecularly similar microbial proteins could be involved. Similarly, in Meniere's disease, several candidate antigens have been identified and used to develop animal models to study autoimmune hearing loss using, for example, type II collagen (CII) (Yoo, T. J., Stuart, J. M., et al., Science, vol. 217, p. 1153-55 (1982) and Yoo, T. J., Tomoda, K., et al., Annal. Otol. Rhinol. Laryngol., vol. 93 (suppl. 113), p. 3-5. (1984)), type IX collagen, c-raf protein (Cheng, K. C., et al., Annal. Otol. Rhinol. Laryngol., vol. 109 (12 Pt. 1), p. 1093-98 (1997)), Po protein (Matsuoka, H., Cheng, K. C., et al., Annals Oto. Rhino. Laryngol., vol. 108 (3), p. 255-64 (1998)) and most recently, β-tubulin (Yoo, T. J., Tanaka, H., et al. Meniere's Disease update, p. 529-535 (1999)).
Autoimmune disorders correspond to irregular immune responses directed at self-tissue. T cells play a central role in the initiation and perpetuation of organ-specific autoimmune disease (Harrison, L. C., Hafler, D. A., Current Opinion in Immunology, vol. 12(2), p. 704-11 (2000)). Because T cells are important mediators in the pathogenesis of autoimmune disease, they are ideal candidates for cell based gene therapy. Several models of autoimmunity involve a Th1-biased progression of immune responses against self antigens, probably responsible for much of the tissue destruction which occurs in autoimmune diseases. Numerous studies have demonstrated successful prevention or amelioration of autoimmune pathogenesis by blocking Th1 cytokines with specific antagonists or by counteracting the inflammatory response with regulatory cytokines (Harrison, L. C., Hafler, D. A.).